Alcohol abuse continues to be a major problem in the United States with an estimated 14 million adults meeting the clinical criteria for a diagnosis of alcohol abuse or alcoholism at an estimated cost of $185 billion. Chronic alcohol exposure has been shown to impact structure and function of the brain but it is unclear when these effects occur since most of what is known of alcohol's effects on the brain is based on studies of individuals who have abused for a long time and the results can be complicated by many factors incuding polydrug abuse, poor nutritional states and other medical conditions. Another complicating factor is the interaction of stress and alcohol. Using magnetic resonance spectroscopic imaging (MRS), we will examine the effects of chronic alcohol self-administration on brain biochemistry in a group of monkeys that have been selected based on their levels of anxiety/cortisol response to novelty. MRS scans will be acquired to determine whether there are differences in the biochemical state of the brains as a function of anxiety state and then as a result of alcohol exposure. We will conduct MRS measures in the ethanol naive state and again following self-administration. We will also track metabolite changes that might occur as a result of normal development or as a result of different cortisol levels in the control animals. We will be in a position to track any changes that occur early in alcohol abuse which is something that cannot be accomplished in human studies. The results will provide some insight into how the brain reacts to stress and alcohol. These data will be collected in the same animals in which high resolution structural scans and cerebral blood flow data will be acquired providing one more crucial piece of data as to how the brain responds to stress and alcohol interactions. We can control all variables associated with alcohol self-administration in these monkeys. They will be monitored both before and after exposure to alcohol, thus, we will be able to monitor the progression of any changes in the biochemical state that directly results from alcohol exposure. These studies will help identify how exposure to long-term alcohol might affect how the brain works. PUBLIC HEALTH RELEVANCE Alcohol (ethanol) abuse and alcoholism are major public health concerns, affecting an estimated 10% of the U.S. population, at an annual cost of over 100 billion dollars. Adequate treatment and intervention strategies continue to elude the medical community in part because the impact of alcoholism on the brain is not clearly understood. The goal of these proposed studies is to better understand how alcohol exerts it effects on brain metabolites with the hope that better insight into alcohol's neurobiological and neurochemical effects will lead to better treatment strategies.